Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (ß = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (ß = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.

Anomalous self-experiences and neurocognitive functioning in adolescents at risk for psychosis: Still no significant associations found between these two vulnerability markers.

BACKGROUND: Anomalous self-experiences (ASEs) and neurocognitive impairments are considered essential domains of vulnerability for developing psychotic disorders. However, little research exists of possible associations between ASEs and neurocognitive functions in individuals at-risk for psychosis. The interconnections between ASEs and neurocognitive impairments should therefore be clarified as much as possible, especially in young individuals at risk. No previous studies have investigated these two fundamental domains in non-help-seeking adolescents at risk for developing psychosis. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). Adolescents (N = 48, 94% females, mean age = 15.3) were invited to participate after completing a 14-year-old survey distributed by MoBA. At-risk adolescents were selected based on the 0.4% highest scores on 19 items assessing both psychotic-like experiences and ASEs. Five specifically selected and formulated items measuring ASEs were computed to an ASEs total score. Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery. RESULTS: Regression analyses revealed no significant relationships between ASEs and any neurocognitive domain. CONCLUSIONS: We did not find any significant associations between ASEs and neurocognitive functions in non-help-seeking adolescents at risk for psychotic disorders, which is in line with reports from other types of cohorts. Thus, ASEs and neurocognitive functions may be understood as two relatively separate domains that co-exist in at-risk states. These results underline the need for a wider scope when making predictions about future trajectories, e.g. the development of psychotic disorders. Including both ASEs and neurocognitive functioning in at-risk populations may increase the specificity of vulnerability criteria in this population and enhance our understanding of early psychosis psychopathology.

A seven-year longitudinal study of the association between neurocognitive function and basic self-disorders in schizophrenia.

Introduction: Basic self-disorders (SDs) and neurocognitive impairments are fundamental trait-like aspects of schizophrenia spectrum disorders. There has been little research on the association between SDs and neurocognitive impairments in schizophrenia, and no longitudinal studies have investigated if they are related. The aim of this study was to investigate the association between SDs and neurocognitive function in a follow-up study of patients with schizophrenia. Methods: SDs and neurocognition were examined in 35 patients with schizophrenia during their first treatment and 7 years later (mean 7.1, SD 0.42). SDs were examined with the Examination of Anomalous Self-Experience (EASE) instrument. The neurocognitive examination included assessments of psychomotor speed, executive- and memory functions. Results: Poorer executive functions at baseline were significantly associated with more SDs 7 years later and smaller reductions in SDs over time. There were no significant associations between other neurocognitive functions and SDs. Discussion: Executive functions are important for self-regulation, and impairments in these functions in everyday life may have an impact on the development and/or persistence of SDs.

Normative modeling of brain morphometry in Clinical High-Risk for Psychosis.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design Setting and Participants: Clinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P individuals [47.09% female; mean age: 20.75 (4.74) years] and 1,237 healthy individuals [44.70% female; mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. Main Outcomes and Measures: For each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of individuals with infranormal (z<-1.96) or supranormal (z>1.96) scores. Results: CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P individuals with infranormal or supranormal values in any metric was low (<12%) and similar to that of healthy individuals. CHR-P individuals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADSSA showed significant but weak associations (|ß|<0.09; PFDR<0.05) with positive symptoms and IQ. Conclusions and Relevance: The study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk.

Linguistic markers and basic self-disturbances among adolescents at risk of psychosis. A qualitative study.

Background: Language impairments are key features of schizophrenia spectrum disorders, and have also been suggested to signal enhanced psychosis risk. Incoherence, derailment, and monotonous speaking are however closely related to psychosis onset, and thus not very early markers. Recent phenomenologic-psychiatric studies claim that basic self-disturbance (BSD) may represent more useful early markers. Methods: We searched for distinctive irregular linguistics of 30 CHR outpatient adolescents, aged 12-18 years. Standard instruments established psychosis risk and BSD. Participants chose three personal and well manifested BSD phenomena. Ninety verbatim statements were analyzed and grouped into higher order clusters of linguistic irregularities. Findings: We identified five clusters of irregular language features: distinctive words, describing an atmosphere of unreality; irregular use of prepositions, indicating experiential detachment; shifts of personal pronouns, indicating identity confusion; near-literal use of metaphors and conjunctions indicating existential insecurity, and idiosyncratic use of adjectives indicating perceptual transcendence. Interpretation: The adolescents provided naturalistic descriptions of experiences that were markedly twisted and almost ineffable. This unique irregular "BSD -language" was highly meaningful in its proper context, expressing informative characteristics of first-personal experiential alterations, essential for early detection. The features may additionally represent precursors of psychosis transition, useful for clinical decision-making. Funding: Foundation Dam, Oslo, Norway (Grant Number 2017/FO143368).

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.

Basic self-disturbance trajectories in clinical high risk for psychosis: a one-year follow-up study.

Basic self-disturbance (BSD) has been proposed as a driver of symptom development in schizophrenia spectrum disorders (SSDs). In a one-year follow-up of 32 patients (15-30 years) at putative risk for psychosis, we investigated trajectories of BSD levels from baseline to follow-up, and associations between clinical characteristics at baseline and follow-up, including follow-up levels of BSD (assessed with the EASE). Clinical high risk (CHR) for psychosis status and symptom severity were assessed with the SIPS/SOPS scales and also according to the cognitive basic symptoms high-risk criteria (COGDIS). DSM-IV diagnoses, functioning and other clinical characteristics were assessed with standard clinical instruments. Higher severity of negative symptoms and meeting COGDIS criteria at baseline were associated with higher BSD levels at follow-up. All measured at follow-up, higher BSD levels correlated with higher severity of positive, negative, disorganization and general symptoms, and with a lower level of global functioning. We found higher BSD levels at follow-up in subjects with schizotypal personality disorder (SPD) at baseline (n = 5) and in SSDs at follow-up (n = 12, including nine with SPD). Mean BSD levels decreased significantly from baseline to follow-up, but individual trajectories varied considerably. Increased BSD levels were associated with higher baseline BSD levels, non-remission of positive symptoms and functional decline. Overall, the current study indicates that subgroups in the CHR population with a higher risk of non-remission or deterioration may be identified by supplementing CHR criteria with assessment of BSD and negative symptoms.

Disordered Selfhood in Schizophrenia and the Examination of Anomalous Self-Experience: Accumulated Evidence and Experience.

Disordered selfhood in schizophrenia was rediscovered at the turn of the millennium. In 2005, Psychopathology published the psychometric instrument, the Examination of Anomalous Self-Experience (EASE). In this article, we summarize the historical background of the creation of the EASE, explicate the notion of the disorder of basic or minimal self with the help of phenomenological philosophy, and provide a brief description of clinical manifestations targeted by the EASE. We also present our personal experience using and teaching the EASE and summarize the empirical evidence obtained so far. We conclude that the basic self-disorder represents a crucial phenotype of schizophrenia spectrum disorders and that this phenotype offers a potential avenue to empirical pathogenetic research and psychotherapeutic treatment.

Basic self-disturbance in subjects at clinical high risk for psychosis: Relationship with clinical and functional outcomes at one year follow-up.

Basic self-disturbance (BSD) is assumed to drive symptom development in schizophrenia spectrum disorders and in clinical high-risk (CHR) for psychosis. We investigated the relationship between BSD at baseline, assessed with the Examination of Anomalous Self-Experience (EASE), and symptoms and functional outcome after one year in 32 patients, including 26 CHR and six with non-progressive attenuated psychotic symptoms. Correlations between baseline BSD levels and positive, negative and disorganization symptoms, and global functioning level at follow-up were significant. Hierarchical regression analyses revealed that higher levels of baseline BSD predicted more severe positive symptoms and lower global functioning at follow-up, after adjusting for baseline positive symptoms and functioning. Subjects who were not in symptomatic and functional remission after one year had higher levels of BSD and negative symptoms, and lower functioning level, at baseline. Baseline BSD in participants with schizophrenia spectrum diagnoses at follow-up (9 of 12 were schizotypal personality disorder) were at the levels seen in schizotypal disorders in previous studies, but not significantly different from the other participants. Early identification and assessment of BSD may constitute a useful prognostic tool and a signal for therapeutic targets in CHR conditions. Further CHR studies investigating these relationships with larger samples are recommended.

Basic self-disturbances are associated with Sense of Coherence in patients with psychotic disorders.

BACKGROUND: The Sense of Coherence (SOC) theory gives a possible explanation of how people can experience subjective good health despite severe illness. Basic self-disturbances (BSDs) are subtle non-psychotic disturbances that may destabilize the person's sense of self, identity, corporeality, and the overall 'grip' of the world. AIM: Our objective was to investigate associations between BSDs and SOC in patients with psychotic disorders. DESIGN: This is a cross-sectional study of 56 patients diagnosed with psychotic disorders inside and outside the schizophrenia spectrum (35 schizophrenia, 13 bipolar, and eight other psychoses). SOC was measured using Antonovsky's 13-item SOC questionnaire, and BSDs were assessed using the Examination of Anomalous Self-Experience (EASE) manual. Diagnosis, symptoms, and social and occupational performance were assessed using standardized clinical instruments. RESULTS: We found a statistically significant correlation (r = ) between high levels of BSDs and low levels of SOC (r = -0.64/p<0.001). This association was not influenced by diagnostics, clinical symptoms or level of functioning in follow-up multivariate analyses. CONCLUSION: A statistically significant association between BSDs and SOC indicates that the presence and level of self-disturbances may influence the person's ability to experience life as comprehensive, manageable and meaningful. However, the cross-sectional nature of the study precludes conclusions regarding the direction of this association.

Basic self-disturbances independently predict recovery in psychotic disorders: A seven year follow-up study.

BACKGROUND: Recovery is the ultimate goal of psychosis treatment. Basic self-disturbances (BSDs) are non-psychotic phenomena associated with clinical outcome, present in prodromal, psychotic and residual phases of psychotic disorders. AIM: To investigate the relationship between BSDs and recovery seven years after first treatment in patients with psychotic disorders. METHOD: Prospective longitudinal study of 56 patients recruited during first adequate treatment for schizophrenia (n = 35) and other psychotic disorders (n = 21) (psychotic bipolar disorder, delusional disorder, psychotic disorder NOS). At baseline and follow-up BSDs were assessed using the Examination of Anomalous Self-Experience (EASE) manual, while standard clinical instruments were used to ascertained diagnosis, clinical symptom severity, and functioning. Recovery was defined as absence of psychotic symptoms and regaining of functioning that persisted the last two years before follow-up. RESULTS: At follow up, 34% achieved recovery (5 (14%) with schizophrenia and 14 (67%) with other psychoses at baseline). Recovery was predicted by an absence of a schizophrenia diagnosis, low baseline level of BSDs and further reductions in BSDs from baseline to follow-up. Change in BSDs was the strongest predictor, also after adjusting for premorbid adjustment and duration of untreated psychosis, and was not confounded by diagnosis. CONCLUSION: Low baseline levels of basic self-disturbances and further reductions over time independently predict recovery seven years later in first treated psychosis patients.

Anomalous self-experiences are strongly associated with negative symptoms in a clinical high-risk for psychosis sample.

OBJECTIVE: Anomalous self-experiences (ASE) are considered as central features of the schizophrenia spectrum disorders and prodromal schizophrenia. We investigated total and single-item prevalence of these phenomena in a clinical high-risk (CHR) for psychosis sample, and associations with conventional psychosis-risk symptoms, present and childhood global/psychosocial functioning, and childhood trauma. METHODS: The sample (n = 38) included 31 CHR, according to ultra-high risk or cognitive basic symptoms (COGDIS) criteria, and seven with non-progressive attenuated positive symptoms. Psychopathological evaluations included the Examination of Anomalous Self-Experience (EASE), Structured Clinical Interview for Prodromal Syndromes (SIPS), Schizophrenia Proneness Instrument - Adult (SPI-A) (only the COGDIS-criteria), a diagnostic interview (SCID-I), Global Assessment of Functioning - Split version (S-GAF), Premorbid Adjustment Scale (PAS) and Childhood Trauma Questionnaire (CTQ). RESULTS: The mean total EASE score was in line with reports from other CHR samples, and was particularly enhanced in schizotypal personality disorder and in subjects fulfilling COGDIS-criteria. The four most frequent EASE-items were present in two-thirds or more of the participants. EASE total was significantly associated with negative and disorganization symptoms. A multiple regression analysis revealed that the level of negative symptoms explained most of the variance in EASE total. CONCLUSIONS: These results corroborates other findings that anomalous self-experiences are frequent and important features in CHR conditions and in the schizophrenia spectrum. The strong associations with negative symptoms and cognitive disturbances (COGDIS) should be investigated in longitudinal studies to address causality, psychopathological pathways and schizophrenia spectrum specificity. The weaker correlation between EASE total and positive symptoms may partly be related to a restricted range of positive symptoms.

Approaching patients with hyperreflectivity and perplexity: an empirical qualitative investigation / Abordando pacientes com hiper-reflexão e perplexidade: uma investigação qualitativa empírica

Abstract Objective Perplexity and hyperreflectivity are considered important aspects of self-disorders in patients with schizophrenia, yet knowledge of the appropriate psychotherapy for these patients is sparse. We aimed to explore how phenomenological psychologists or psychiatrists described their approach to these patients and their own emotional response when hyperreflectivity and perplexity emerged in therapy or consultations. Methods Four e-mail interviews with experienced clinical researchers within the field of phenomenology and schizophrenia were examined using a double hermeneutic qualitative analysis. Results The informants offered reassurance by authority and the encouragement of sharing of experiences interlaced in the beginning of therapy. Later they went on relating expressions of hyperreflectivity and perplexity to emotions, life events and goals. They described feelings of admiration and professional recognition along with worry, insecurity and sadness. Conclusion The list of primary themes covers what might seem very basic therapeutic interventions. However, the careful and open-minded manner in which these were carried out was noteworthy. The double task of staying closely attuned to the patient's airy reflections and, at the same time, when the patient was ready for it, carefully making links to domains of the patient's everyday life, was clearly molded to patients with fragile attachment.

Resumo Objetivo A perplexidade e a hiper-reflexão são consideradas aspectos importantes dos desordens do self em pacientes com esquizofrenia, porém o conhecimento sobre o tipo mais apropriado de psicoterapia para esses pacientes é escasso. Nosso objetivo foi explorar como psicologistas fenomenológicos ou psiquiatras descrevem suas abordagens a pacientes aos pacientes e sua própria resposta emocional, quando a hiper-reflexão e a perplexidade emergem durante a terapia ou as consultas. Métodos Quatro entrevistas feitas por e-mail com pesquisadores clínicos experientes na área de fenomenologia e esquizofrenia foram examinadas usando análise qualitativa dupla hermenêutica. Resultados Os informantes ofereceram confiança via autoridade e motivação para compartilhar experiências, interligadas, no início da terapia. Subsequentemente, eles seguiram relacionando expressões de hiper-reflexão e perplexidade a emoções, eventos de vida e objetivos. Eles descreveram sentimentos de admiração e reconhecimento profissional juntamente com preocupação, insegurança e tristeza. Conclusão A lista de tópicos primários engloba o que poderiam parecer intervenções terapêuticas muito básicas. No entanto, a forma cuidadosa e aberta como essas intervenções foram conduzidas é digna de nota. A tarefa dupla de estar atento às reflexões aéreas do paciente e, ao mesmo tempo, quando o paciente está pronto, cuidadosamente estabelecer relações com os domínios de sua vida diária, foi claramente moldada para pacientes com vínculo frágil.

Stability in basic self-disturbances and diagnosis in a first treated psychosis: A seven year follow-up study.

BACKGROUND: Basic self-disturbances (BSDs) are considered core features of schizophrenia spectrum disorders, and are present in the prodromal, early psychotic and chronic phases. Considerable levels of BSDs are also present at first treatment in some patients with psychotic disorders outside the schizophrenia spectrum. There is limited knowledge about the stability of self-disturbances over time. AIM: To explore the stability of BSDs in a seven-year follow-up of first treatment patients, and the association between baseline levels and changes in BSDs and diagnostic changes at follow-up. METHOD: Longitudinal study of 56 patients (35 schizophrenia and 21 non-schizophrenia) recruited at their first treatment for a psychotic disorder. BSDs were assessed using the Examination of Anomalous Self-Experience (EASE), while diagnostic categories, clinical symptom severity, and functioning were assessed with standard clinical instruments. RESULTS: The schizophrenia group had significantly lower levels of BSDs at follow-up compared to baseline. The EASE domain "Cognition and stream of consciousness" was the most stable. There were no diagnostic changes into or out of schizophrenia spectrum. Patients with schizophrenia had significantly higher levels of BSDs both at baseline and at follow up than patients with psychotic disorders outside the schizophrenia spectrum, who showed stable low levels. CONCLUSION: We found a decrease and thus less stability in BSDs in schizophrenia than expected. This might indicate that BSDs tent to weaken over time, and that unknown individual characteristics may influence the development of BSDs. Diagnostic stability from baseline to follow-up may be due to long DUP before service entry.

Approaching patients with hyperreflectivity and perplexity: an empirical qualitative investigation.

OBJECTIVE: Perplexity and hyperreflectivity are considered important aspects of self-disorders in patients with schizophrenia, yet knowledge of the appropriate psychotherapy for these patients is sparse. We aimed to explore how phenomenological psychologists or psychiatrists described their approach to these patients and their own emotional response when hyperreflectivity and perplexity emerged in therapy or consultations. METHODS: Four e-mail interviews with experienced clinical researchers within the field of phenomenology and schizophrenia were examined using a double hermeneutic qualitative analysis. RESULTS: The informants offered reassurance by authority and the encouragement of sharing of experiences interlaced in the beginning of therapy. Later they went on relating expressions of hyperreflectivity and perplexity to emotions, life events and goals. They described feelings of admiration and professional recognition along with worry, insecurity and sadness. CONCLUSION: The list of primary themes covers what might seem very basic therapeutic interventions. However, the careful and open-minded manner in which these were carried out was noteworthy. The double task of staying closely attuned to the patient's airy reflections and, at the same time, when the patient was ready for it, carefully making links to domains of the patient's everyday life, was clearly molded to patients with fragile attachment.

Anomalous Self-Experiences: Markers of Schizophrenia Vulnerability or Symptoms of Depersonalization Disorder? A Phenomenological Investigation of Two Cases.

BACKGROUND: Basic self-disturbance (BSD) is proposed to constitute the clinical core of schizophrenia spectrum disorders, including prodromal states and schizotypy. Anomalous self-experiences (ASEs) are suggested as phenotypic variants of BSD, representing markers of schizophrenia vulnerability. However, ASEs are not restricted to the schizophrenia spectrum, but may also occur in non-psychotic states like depersonalization disorder (DPD). It is unclear to what extent the prevalence and nature of ASEs are differing between the two conditions. The main aim of this paper is to assess and compare ASEs in both conditions, based on literature and two illustrating cases. This might expand the understanding of these phenomena, and strengthen the basis for clinical differentiation. METHODS: One patient with schizotypal personality disorder (SPD) and one with DPD were selected from an ongoing clinical high-risk (CHR) for psychosis study. ASEs were assessed with the Examination of Anomalous Self-Experience (EASE) and analyzed according to the two central dimensions of BSD: diminished self-affection and hyperreflexivity, as well as according to prototypical aspects of depersonalization. The cases were also analyzed and compared with respect to chronology, other symptomatology, and psychopathological pathways. RESULTS: Both cases revealed ASEs reflecting the central dimensions of BSD as well as prototypical aspects of depersonalization. Only the SPD case however, linked ASEs to psychotic-like ideas of external influence and control. The symptoms had an insidious early childhood onset with no obvious triggers in the SPD case, and an abrupt adolescence onset triggered by second-time cannabis use and panic anxiety in the DPD case. CONCLUSIONS: The similarities and differences in ASEs, symptomatology and developmental pathways of the two cases might be accounted for by an updated model of self-disorders. The model proposes that schizophrenia manifests as a result of a combination of early "primary"-onset ASEs, reflecting dis-turbances in early neurodevelopment, and later occurring, "secondary" ASEs of a more defensive-protective character. In line with this, the DPD case may be characterized only by secondary ASEs and thus better protected against psychotic decompensation than the SPD case, tentatively affected by a combination of primary and secondary ASEs.

High levels of anomalous self-experience are associated with longer duration of untreated psychosis.

AIM: To investigate the relationship between anomalous self-experiences and duration of untreated psychosis in a sample of patients with first-episode schizophrenia spectrum disorders. METHODS: Anomalous self-experiences were assessed by means of the Examination of Anomalous Self-Experience manual in 55 patients referred to their first adequate treatment for schizophrenia. Diagnoses, symptom severity, functioning and childhood trauma were assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale, Premorbid Adjustment Scale, Social Functioning Scale and Childhood Trauma Questionnaire. Substance misuse was measured with the Drug Use Disorder Identification Test, and alcohol use was measured with the Alcohol Use Disorder Identification Test. Duration of untreated psychosis was measured in accordance with a standardized procedure. RESULTS: High levels of anomalous self-experiences are significantly associated with longer duration of untreated psychosis, an association which held after correcting for other variables associated with long duration of untreated psychosis. CONCLUSIONS: The field of early detection in psychosis is in need of additional clinical perspectives to make further progress. Improved understanding and assessment of anomalous self-experiences may help clinicians to detect these important phenomena and provide earlier help, and thus reduce treatment delay.

The Association between Anomalous Self-experiences, Self-esteem and Depressive Symptoms in First Episode Schizophrenia.

Background: Anomalous self-experiences (ASEs) aggregate in schizophrenia spectrum disorders, but the relationship between ASEs, and depression has been studied to a limited extent. Lower self-esteem has been shown to be associated with depression in early psychosis. Our hypothesis is that ASEs in early phases of schizophrenia are linked to lower levels of self-esteem, which in turn is associated with depression. Aim: The aim is to examine the relationship between ASEs, self-esteem and depression in first-episode schizophrenia spectrum disorders. Method: ASEs were assessed in 55 patients with first-episode schizophrenia by means of the Examination of anomalous Self-Experience (EASE) instrument. Assessment of depression was based on the Calgary Depression Scale for Schizophrenia (CDSS). Self-esteem was measured using the Rosenberg Self-Esteem Scale (RSES). Symptom severity was assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale (SCI-PANSS). Substance misuse was measured with the Drug Use Disorder Identification Test (DUDIT), and alcohol use was measured with the Alcohol Use Disorder Identification Test (AUDIT). Data on childhood adjustment were collected using the Premorbid Adjustment Scale (PAS). Data on childhood trauma were collected using the Norwegian version of the Childhood Trauma Questionnaire, short form (CTQ-SF). Results: Analyses detected a significant association between current depression and ASEs as measured by the EASE in women, but not in men. The effect of ASEs on depression appeared to be mediated by self-esteem. No other characteristics associated with depression influenced the relationship between depression, self-esteem and ASEs. Conclusion: Evaluating ASEs can assist clinicians in understanding patients' experience of self-esteem and depressive symptoms. The complex interaction between ASEs, self-esteem, depression and suicidality could be a clinical target for the prevention of suicidality in this patient group.

Collaborative Assessment and Management of Suicidality (CAMS) compared to treatment as usual (TAU) for suicidal patients: study protocol for a randomized controlled trial.

BACKGROUND: Collaborative Assessment and Management of Suicidality (CAMS) is a therapeutic framework that appears promising to reduce suicidal ideation and suicidal cognition. CAMS has not previously been evaluated in a standard specialized mental health care setting for patients with suicidal problems in general. In this pragmatic randomized controlled trial (RCT) we will investigate if CAMS is more effective than treatment as usual (TAU) in reducing suicidal thoughts and behaviors. Effects will also be investigated on mental health and symptom relief in general and upon readmissions to inpatient units. METHODS/DESIGN: The study is a multicenter, observer-blinded, superiority, two-armed RCT which will include patients from four clinical departments at Vestre Viken Hospital Trust, Norway. We aim to include 100 patients with moderate to strong suicidal problems, as defined by a score of 13 or more on Beck's Scale for Suicide Ideation - Current. Patients are included regardless of diagnosis. Randomization will be performed using a stratified four-block procedure with treatment unit as the stratification variable. The duration of treatment will vary depending on patients' needs and clinical assessments. Patients are interviewed by research staff at four checkpoints: baseline, 2 weeks, 6 months, and 12 months. Central outcome measures are the Beck Scale for Suicide Ideation - Current, Outcome Questionnaire - 45, and Suicide Attempt Self-Injury Count. DISCUSSION: This pragmatic trial is effectuated within the Public Health Care System in Norway, where patients have multiple problems and diagnoses and therapists have a high work load. Results from this trial are highly generalizable to a typical everyday clinical setting, and one should expect similar results if CAMS is implemented in the future as a standard component in specialized mental health care systems. TRIAL REGISTRATION: Open Science Framework: DOI 10.17605/OSF.IO/JHRM2 . Registered 5 July 2015. ClinicalTrials.gov: NCT02685943 . Registered on 8 February 2016.